This program project is a multidisciplinary, translational research project employing animal and human projects to focus on the elucidation of neurobiological and behavioral characteristics and responses of mothers that have used primarily cocaine during pregnancy and of offspring prenatally exposed to cocaine that might impact negatively on normal mother-infant interactions. Although maternal cocaine use is known to be highly correlated with maternal neglect and poorer mother-infant interactions in both human and animal models, there is little direct research on perceptual, endocrine and neurological responses of these women when presented with relevant infant cues (cries, touch, pictures). Similarly, little is known about abnormal physiological/behavioral responses in infants prenatally exposed to cocaine that may impact parenting behaviors of both drug using and non-using mothers. One animal, and 2 human clinical projects will address three main hypotheses which address the possibility that cocaine use by mothers and/or prenatal exposure to cocaine in offspring could result in drug-induced neurological and/or bio-behavioral abnormalities in both, that contribute to neglect and poor mother-infant interactions in animals and humans. The animal project will assess specific characteristics of infant stimuli or behavior (vocalizations, thermoregulatory ability, olfactory cues, response to mothers presence) and brain structural abnormalities (regional, ventricular differences) and gene expression as well as measuring differential maternal behavioral and endocrine responses to and preference for exposed compared to non-exposed infants or stimuli produced by infants. The human projects will focus on perceptual, endocrine and behavioral responses to stress related and infant related stimuli and infant response to mothers, as well as infant brain structural and pathway developmental abnormalities (project 2) and (project 3) measurement of maternal (fMRI) endocrine and neurological brain regional responses to infant stimuli (cries, visual vignettes). We hypothesize differences in behavioral, physiological and/or neurological characteristics (infant cries, infant stimulus cues, physical elicitation of care and brain structural abnormalities) of both human and rodent offspring (prenatally drug exposed versus non-exposed), which could result in differential maternal response. We predict that mothers who have abused cocaine will exhibit differences in perceptual, behavioral, endocrine and/or neurological responses to relevant infant stimuli compared to non-drug users. This translational, interdisciplinary project will allow researchers from different research backgrounds and expertise to work together to better identify specific attributes of mothers and infants that could contribute to a better understanding of how drugs of abuse specifically and particular characteristics of individuals in general may influence neglect. This could result in early and continuing intervention strategies to offset some of the negative consequences in this population.